Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to endocrine therapy

Abstract

Summary Northern hybridization analyses of the oestrogen-inducible mRNAs pLIV1 and pS2 were compared with oestrogen receptor (ER) immunocytochemistry assessments in 40 untreated primary or early recurrent breast tumours. Significant associations were observed between pLIVl/ER (P < 0.03), pS2/ER (P < 0.001) and pLIV1/pS2 (P < 0.04) status. After disease recurrence, patients were treated with assessable courses of endocrine therapies. Positive pLIV1, pS2 and ER statuses in primary disease were consequently found to be predictive of endocrine responsiveness in the secondary lesions (P < 0.03, P < 0.02, P < 0.005 respectively). However, despite these associations, a number of pLIV1i-and/or pS2-positive tumours failed to respond to therapy.Keywords: oestrogen-regulated genes; breast cancer; oestrogen receptor The selection of breast cancer patients for endocrine therapy is most frequently made on the basis of tumour oestrogen-receptor (ER) protein content. However, the predictive capability of ER status alone is not absolute (Nicholson et al, 1991). While few ERnegative patients respond to such therapies, perhaps half of ERpositive patients will also gain no clinically defined benefit. It has been postulated that coassessment of ER and oestrogeninducible genes or protein products, as markers of functioning ER-mediated cellular growth mechanisms, might give better predictive results. As such, the additional measurements of tumour PR and pS2 protein content have been shown to partly improve selectivity (Horwitz and McGuire, 1977;Foekens et al, 1990).Our study evaluates the significance of expression of the oestrogen-inducible pLIVl (Manning et al, 1988) 13 as grade 2 and 22 as grade 3. Twenty-seven tumours were described as infiltrating ductal (no special type), five mixed/tubular, two mixed ductal/lobular and the remainder as single cases of lobular, medullary, atypical medullary, mixed ductal/mucinous and ductal carcinoma in situ.

LIV-1 Promotes Prostate Cancer Epithelial-to-Mesenchymal Transition and Metastasis through HB-EGF Shedding and EGFR-Mediated ERK Signaling

“…With regard to the mechanism of interconversion between epithelial and mesenchymal phenotypes through EMT and MET, it is interesting to note that increased LIV-1 expression can be achieved by hormonal induction [3], [8] and by growth factor engagement (Figure 1). It is conceivable that with induction of LIV-1, cancer cells can establish metastatic foci through EMT that confers increased migratory and invasive capabilities.…”

Zinc and Cancer: Implications for LIV-1 in Breast Cancer

“…Work by McClelland et al (1998) demonstrated that detection of LIV-1 can be used to signify a patient’s positive response to endocrine therapy [182]. Due to its induction by estradiol, LIV-1 has been proposed to be a marker gene to assay ER+ breast cancer in vivo .…”

Expression levels of the putative zinc transporter LIV‐1 are associated with a better outcome of breast cancer patients

“…In some patients, LIV‐1 expression correlates with the response to endocrine therapy 3. Treatment with anti‐estrogens before primary breast surgery has no effect on LIV‐1 mRNA expression, however, despite changes in ER protein levels 4.…”